Fluidic Interfacing System and Assembly

ABSTRACT

A fluidic assay system assembly comprising: (a) A disposable fluidic cartridge ( 1 ) comprising at least one reaction chamber ( 3 ) connected to a network of fluidic channels ( 2 ) with at least one inlet channel and one outlet channel. The said inlet and outlet channels end at the down side of the fluidic cartridge with at least two connecting pores ( 4 ), ( 4′ ); (b) A disposable vessel ( 5 ) comprising a connection tube  22  immersed in a sample container ( 6 ) and ended at the cap of the vessel with an external connection pore ( 7 ) ; (c) A fluidic manifold ( 8 ) that is interdependent with the bulk system ( 12 ) comprising a fluidic network connected ( 9 ) to active fluidic parts ( 10 ), ( 11 ). The said channel network ends at the top side of the fluidic manifold with at least one connecting pore ( 13 ). Wherein the first and the second pores of the fluidic cartridge are interfaced by direct physical contact with the sample container and the manifold pores, respectively.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a Continuation of U.S. patent application Ser. No.13/700,644, which is a national stage application, filed under 35 U.S.C.§371, of International Application No. PCT/1B2011/052440, filed Jun. 3,2011, which claims the benefit of and priority to Swiss PatentApplication No. 00885/10, filed Jun. 3, 2010. The contents of eachapplication are incorporated by referenced in their entirety.

FIELD OF THE INVENTION

The invention relates to a system for conducting an automated assay on aspecimen which contains specific biological or chemical substances thatneed to be detected. More specifically, the invention discloses a devicethat includes a fluidic cartridge and the interfacing of the saidcartridge with the sample and the different reagents used in performingsuch assay.

BACKGROUND OF THE INVENTION

The testing of diverse sample types derived from human, animal, plantsources, food and environmental samples plays a crucial role in modernmedical diagnosis and treatment, forensic medicine, food safety,industrial processing among many other fields. However, such analysesare very often related to complex processes that relate tolabor-intensive, chemical, biological and physical steps on a fluidsample that will end in the detection of specifically targeted moleculesor analytes using optical, electrical and biochemical procedures. In thecurrent state-of-the-art, sample analysis steps remain mainly dominatedby complex, large and expensive “robotic” instruments operated by experttechnicians in centralized laboratories. Consequently, any technologythat would automate the complex reaction and sample processing stepswhile making them more affordable and less space-consuming would addressunmet needs for simple, cost-effective assaying solutions.

As an emerging alternative to the robotic platforms, fluidic ormicrofluidic technologies open new perspectives in assay processing andautomation. In relation to recent developments in molecular biology,nanotechnology and optics, (micro)-fluidic based systems comprehendindeed the potential of providing integrated solutions, where all stepsfrom sample preparation and assay processing to signal amplification anddetection of multiple targets will be integrated in a fully automated,compact cartridge.

A typical example of a commercially available cartridge-based solutionis the

GeneXpert molecular diagnostics platform from Cepheid (CA, USA)(cepheid.com) which realized an advance in fully automated moleculartesting from sample input to result reporting. As for instance disclosedby the U.S. Pat. No. 6,893,879, U.S. Pat. No. 6,664,104, U.S. Pat. No.6,818,185 and U.S. Pat. No. 6,783,736, the Cepheid system demonstratesthe integration of micro-fabricated chips and other miniaturized fluidicor analytical components in a cartridge type where steps from theseparation of a desired analyte from the original sample fluid sample toassay processing and target detection are being performed.

Beyond the integration capabilities, one fundamental issue of thedevelopment of a micro-fluidic based system is the interfacing of thefluidic part which is substantially small and compact as compared to therelatively large macro-environment, as defined by the user samples,reagents and sensing elements.

With this respect, the international Pat. Application WO 2008/030433 forinstance describes the use of a cartridge, which is adapted to containsamples and reaction fluids to interface with a micro-fluidic chip foruse for DNA analysis tests and other assays performed within themicro-fluidic chip. The microfluidic interface is assured through accessports in connection with microfluidic channels and located on the topside of the associated micro-fluidic chip. The reagents and samplescontained in external chambers within a fluidic cartridge are dispersedinto the microfluidic chip through nozzles that will be brought incommunication with the access ports on top of said microfluidic chip.Within the same spirit, WO 2010/118427 discloses a fluidic interfacedevice that includes a cartridge with microfluidic configuration that isin fluid communication with a microfluidic chip through contact pores.

The state-of-the-art coupling and interfacing of the micro-fluidic basedsystem with the external environment systems, are facing however a realchallenge: The integration of maximum functionalities within themicro-fluidic cartridge which leads to a complex and costly “disposable”cartridge or to lower integration properties at the cartridge levelresulting in a more complex interfacing device that practically end incomplex robotic platforms. The optimal balance between the cartridgecomplexity/simplicity versus the corresponding interfacing systemsimplicity/complexity is still an open mostly unresolved issue.

In knowledge of these shortcomings the current invention concerns asystem for conducting automated assays within a fluidic cartridge andits interfacing device on a sample containing specific biological orchemical substances that need to be detected. This disclosed systemovercomes various limitation and constraints by assuring the simplicityof both the disposable cartridge and its interfacing system.

SUMMARY OF THE INVENTION

The present invention provides a system for the automated procedure ofbio-chemical assays that includes:

-   -   a. A disposable fluidic cartridge comprising at least one        reaction chamber connected to a network of fluidic channels with        at least one inlet and one outlet channels, wherein the said        inlet and outlet channels end at the down side of the fluidic        cartridge with at least two connecting pores;    -   b. A disposable vessel comprising a connection tube immersed in        a sample container and ended at the cap of the vessel with an        external connection pore;    -   c. A fluidic manifold that is interdependent to the bulk system        comprising a fluidic network connected to active fluidic parts,        wherein the said channel network ends at the top side of the        fluidic manifold with at least one connecting pore; and        wherein the first and the second pores of the fluidic cartridge        are interfaced by direct contact with the sample and the        manifold container pores respectively.

The key advantage of this invention is the simplicity of the automatedsystem in managing the sample as well as the different reagents thatwill be used in any assay process.

This simplicity is first translated by the fluidic cartridge design thatcan be composed from plastic molded parts preferably comprising of astructured layer with fluidic structures and of a sealing layer. In apreferred realization of the invention, the closing-down layer iscomposed of an elastomeric material which in practice will serve as aninterface to seal the connection of the fluidic cartridge pores with therespective pores of the disposable vessel and fluidic manifold.

Accordingly, the present invention discloses a fluidic cartridge forassaying target biomolecules or particles from a crude sample, thecartridge comprising of:

-   -   d. at least one structure top layer containing:        -   i. a reaction chamber with a solid support that is designed            to capture the said target biomolecules,        -   ii. a first inlet and outlet channels that are in fluid            communication with the said reaction chamber and that will            be used to bring the sample it and out the reaction chamber,        -   iii. a second inlet and outlet channels connected to the            said reaction chamber and will be used for eluting the            purified biomolecules,        -   iv. wherein the second inlet and outlet channels are            diverging branch of the first inlet and outlet channels,    -   e. a closing down layer composed from a flexible material and        comprising connection pores associated to the ends of the said        inlets and outlets channels,

Further, the simplicity of the automated system is realized by handlingthe sample to be assayed within a disposable sample vessel containerfrom a traditional laboratory sample collection tube with a pierceablecap. To assure the connectivity with the fluidic cartridge a syringeadapter is inserted into the tube. Such tubes will be preferably usedfor containing the starting sample that will be assayed and therebyavoid the complexity induced by the integration of sample storingdirectly into the fluidic cartridge.

Further, the simplicity of the automated system is realized by a fluidicmanifold that comprises fluidic network channels and active fluidicelements like valves and pumps mounted on the said manifold. The fluidicmanifold according to the invention is further characterized by the factthat it is part of the bulk system. Fluidic connectivity of the fluidicmanifold with the disposable fluidic cartridge is assured throughconnection pores disposed on the top side of the manifold and that willbe directly in contact with the fluidic cartridge and the poresreflectively. Furthermore, the fluidic manifold comprises connectionpores that will be in a fluidic communication with the diverse assayingreagents. The latter will be transported through the fluidic manifoldnetwork channels to be thereafter injected into the fluidic cartridgethrough a specifically dedicated pore. To avoid cross contamination, themanifold fluidic network channels are divided into a first networksegment of channels specifically designed to handle the sample to beassayed and a second segment of channels specifically designed to handlethe reagents and wherein the said first and second segment of channelsare fluidically disconnected from each other.

In summary, the current invention discloses a fluidic system assemblyfor conducting bio-assays comprising of:

-   -   (1) A fluidic cartridge plastic element in which the assay will        be conducted. Without any active element integration, this        disposable element can be easily manufactured using standard        plastic injection molding and assembling techniques. Designed        for specific assays, the cartridge can further include assay        specific reagents as specific affinity or detection reagents        preferably in a lyophilized format.    -   (2) A sample container and handling vessel that must be also        disposable to avoid any cross-contaminations. Rather than to be        directly integrated into the fluidic cartridge, the sample        container according to the invention is a standard laboratory        tube with a pierceable cap. To assure the fluidic connectivity,        preferably, a syringe adapter is inserted in the tube through        the said pierceable cap.    -   (3) A fluidic manifold that contains the system active elements        (valves, pumps, actuation and sensing elements) will be        integrated. This part of the system is not disposable and will        be considered as part of the bulk of the system. The fluidic        manifold can also directly integrate the generic reagents        handling to avoid cross contamination issues.    -   (4) The manifold as well as the sample containers will be        directly interfaced with the fluidic cartridge through the        respective pores disposed at the down layer of the said fluidic        cartridge. The fluidic manifold can also serve as support to        receive the sample vessels. The microfluidic chip will be on the        top of the fluidic manifold and the sample vessel to provide the        full fluidic sealed assembly.

BRIEF DESCRIPTION OF THE DRAWINGS

The objects and features of the present invention are set forth withparticularity in the appended claims. The present invention, both as toits organization and manner of operation, together with further objectsand advantages, may best be understood by reference to the followingdescription, taken in connection with the accompanying drawings, wherein

FIGS. 1 is a schematic representation of the fluidic assembly andsamples interfacing according to a preferred embodiment of theinvention.

FIGS. 2 is a schematic representation of the fluidic cartridge accordingto a preferred embodiment of the invention.

FIG. 3 shows a schematic view of a system realization that includes thekey features of the invention. The system design, components and theconnectivity of such components are shown in accordance with thepreferred embodiments of the invention.

FIG. 4 shows a schematic representation of the system of the FIG. 3after the different components of the system have been assembled.

FIG. 5 shows a schematic representation of the system of the FIG. 4 withan emphasis of the disposable vessels and the fluidic manifold assemblyaccording to a preferred embodiment of the invention.

FIG. 6 is a schematic representation of the disposable vessels accordingto a preferred embodiment of the invention.

FIG. 7 is a schematic representation of the liquid position sensingwhich comprises a fluidic cartridge with a reaction chamber and at leastone optical sensor positioned on one side of the said reaction chamber.

FIG. 8 is schematic representation of the liquid position sensing methodaccording to the invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The main purpose of the present invention is an automated system forsample handling, preparation and assaying using a disposable of a simpledesigned and low cost fluidic cartridge. Furthermore, the inventiondiscloses an interfacing system of the said cartridge with the sample tobe assayed and also with the reagents used in performing such assay.Another main attainable objective of the present invention is a fullyautomated device for biological liquid sample and reagent processing ina microfluidic using the said fluid cartridge and the relatedinterfacing system.

In general, the microfluidic environment of the invention concernsdevices typically designed at a scale suitable to analyze micro-volumespreferably in the range 0.1 ml to 500 μl. However, for one of the majorapplications of the invention large sample sizes are used to concentratespecific biomolecules or biological cells or particles in the device toa small volume for subsequent analysis. The microscale flow channels andwells have preferred depths and widths in the order of 0.05-1 mm. The“reaction chamber” that is part of the microfluidic network as usedherein refers to chambers with a cavity that have a volume in the rangeof 1 μl to 1 ml and preferably in the range 10 μl to 200 μl. However,for many applications, larger “mesoscale” dimensions in the scale ofmillimetres may be used. Similarly, geometry features often will havelarger dimensions than the microchannels, in the scale of 1-10 mm widthand 1-5 mm depth.

The disclosed system and devices herein can be applied to performcomplex assays used in various testing laboratories and clinicalprocedures. Such procedures can include but are not limited toextraction, purification and concentration of target molecules orparticles from a wide range of target substances in biological samples.Examples of target substances are cells, cell components, cellsubpopulations (both eukaryotic and prokaryotic), bacteria, viruses,parasites, antigens, specific antibodies, nucleic acid sequences and thelike. Furthermore, such assay procedures can include the steps withoutlimitation of labeling, amplifying and detecting such target moleculesor particles. In particular, detection procedures including, but notlimited to polymerase chain reaction (PCR), real-time PCR, ligase chainreaction (LCR), strand displacement amplification (SDA), and nucleicacid sequence based amplification (NASBA).

The present invention provides a system for automated performance ofbio-chemical assays that includes a disposable fluidic cartridge (1)comprising of at least one reaction chamber (3) connected to a networkof fluidic channels (2) with at least one inlet and one outlet channel.The said channels end at the down side of the fluidic cartridge with atleast two connecting pores (4), (4′).

This simplicity is first translated into the fluidic cartridge designthat can be composed from a plastic molded parts comprising, as shown inFIG. 1, from at least one layer 1(a) with fluidic structures and asealing layer 1(b). In a preferred realization of the invention, theclosing down layer is composed from a flexible polymeric material. Withthis respect, the flexible closing layer is preferably composed from anelastomer and more preferably from a thermoplastic elastomer. For thefluidic cartridge working, the said flexible polymeric material formingthe lower side of the fluidic cartridge will further serve as aninterface (16) to seal the connection of the fluidic cartridge pores(4′), (4′) with the respective pores of the disposable vessel (7) andfluidic manifold (13).

The structured layer of the fluidic cartridge 1(a) comprises the fluidicnetwork and the reaction chamber according to the invention. The layoutof a preferred realization of such structured layer is shown in FIG. 2.The structured layer is composed from a fluidic channel network (2)connected to a reaction chamber (3). This connection is operated throughan inlet and outlet channel (25in) and (25out) respectively. The fluidicchannel network ends at the down sides of the chips in connection pores(4).

Operation of the fluidic cartridge as shown in FIG. 2 consists ofaspirating the sample within the sample vessel (5) connected to the pore(4′a), into the reaction chamber (3) through the inlet channel (25in).This is achieved using an active pump connected to the outlet channel(25out) through a connection pore (4 b). After being processed in thereaction chamber, the sample can be transferred to a waste container(15) connected to the manifold through a connection pore (13′) as shownin FIG. 1.

The fluidic cartridge according to another preferred embodiment of theinvention further comprises a second sample connection pore (4′b)connected to the reaction chamber (3) through a second outlet channel(26out). The second outlet channel (26out) forms a diverging branch ofthe first inlet channel (25in). In operating conditions, the connectionpore (4′b) is directly connected to a recovery sample vessel (5′) (asshown in FIG. 3) that will be used to recover the reaction product(s)from the reaction chamber through the outlet channel (26out). This canbe assured by pushing air using a second active pump element connectedto a second inlet channel (26in) of the reaction chamber through asecond connection pore (4 a) and wherein the said second inlet channel(26in) forms a diverging branch of the first outlet channel (26out). Asa typical example, but not limited to, the recovered material cancomprise purified bio-molecules as nucleic acids or proteins.

The fluidic cartridge according to the invention further comprises aninjection pore (4′c) through which different generic reagents, like butnot limited to washing, lysis, binding or detection reagents, can betransferred to the reaction chamber by the aspiration pump connected tothe pore (4 b).

According to a preferred embodiment of the invention, the reactionchamber contains a solid support with an active surface to attach orcapture target molecules or particles carried by the sample. The saidsolid support includes but not limited to particles (preferablymagnetic) or porous matrix.

From the preceded, the invention discloses a fluidic cartridge forpurifying target biomolecules from a sample that comprises:

-   -   (a) at least one structure top layer containing:        -   i. a reaction chamber (3) with a solid support that is            designed to capture the said target biomolecules,        -   ii. a first inlet (25in) and outlet (25out) channel that are            in fluid communication with the said reaction chamber and            that will be used to bring the sample into and out of the            reaction chamber,        -   iii. a second inlet (26in) and outlet (26out) channel            connected to the said reaction chamber and that will be used            for eluting the purified biomolecules        -   iv. wherein the second inlet and outlet channels are            diverging branches of the first inlet and outlet channels,    -   (b) a closing down layer composed from a flexible material and        comprising connection pores associated to the ends of the said        inlet and outlet channels.

In a preferred embodiment, the closing down layer of the fluidiccartridge further can be used as an elastic membrane (27) that can bedeformed using an external actuation to seal one specific channel andthereby prevent the flow through the said channel. This is particularlyimportant in operating the chip, where by using this valve mechanism itallows for instance to seal the recovery channel (26out) or the sampleinlet channel (25in) during the sample aspiration out of the sample tube(5) into the reaction chamber (3) or the eluate sample recovery fromthis reaction chamber into the recovery tube (5′) respectively.

Accordingly, the present invention further provides a system forautomated conducting of bio-chemical assays that includes at least onedisposable vessel (5) comprising of a connection tube (22) immersed in asample container (6) and ending at the cap of the vessel with anexternal connection pore (7 a).

Rather than to be directly integrated into the cartridge, the simplicityof the systems consists of the use a disposable sample vessel container(5) composed from a traditional laboratory sample collection tubes (25)with a pierceable cap (23). To assure the connectivity with the fluidiccartridge a syringe adapter (22) is inserted into the tube. It will beobvious for a person having ordinary skills in the art that the samplecontaining vessel can be alternatively manufactured as one piece withthe connection tube already integrated into the vessel core.

In a preferred embodiment, such tubes will be preferably used forcontaining the starting sample that will be assayed.

Preferably also, the collection tube according to the invention can beused as a tube (5′) for recovering specific molecules as for instancepurified bio-molecules or particles after their separation in thefluidic cartridge. In this particular context, the recovery tube can bealso used as an intermediary tube that can contain a specific liquidthat will further react with the sample after being eluted out of thereaction chamber. Such reaction can include but not limited to, abuffering re-adaptation reaction, enzymatic reaction, targetamplification reaction and a detection reaction. Furthermore, afterreacting within the said recovery tube, the resulting reactant canfurther be pumped out into the fluidic cartridge for further assayprocessing steps.

In a preferred embodiment according to the invention, the automatedsystem assembly for conducting bio-chemical assays can further includeat least one disposable vessel (5′) ending at the cap of the vessel withan external connection pore (7 b) and that can be used for recoveringreactants as purified bio-molecules out of the fluidic cartridge. Thedifference of this tube as compared with the tube according to thepreceding embodiments is that the reactant cannot be further pumped outinto the fluidic cartridge for further assay processing steps.

Accordingly, the present invention further provides a system for theautomated performance of bio-chemical assays that includes a fluidicmanifold (8) that is part to the bulk system (12) comprising of afluidic channel network (9) and active fluidic components (10), (11).The said channel network ends at the top side of the fluidic manifoldwith at least one connecting pore (13) and wherein the first and thesecond pore (4′), (4) of the fluidic cartridge are interfaced by directcontact with the sample (7) and the manifold (13) container poresrespectively.

In a preferred embodiment, the fluidic manifold (8) comprises of afluidic network channels (9) and of active fluidic elements like valves(11) and pumps mounted on the said manifold (10). The fluidic manifoldaccording to the invention is further characterized by the fact that itis part of the bulk system (12). Fluidic connectivity of the fluidicmanifold (8) is assured through connection pores (13) disposed on thetop side of the manifold. The said connection pores (13) are designed ina way to be aligned with corresponding connection pores (4) positionedon the down side of the fluidic cartridge. With this respect and asshown in FIG. 5, the manifold pores (13 a), (13 b) and (13 c) will berespectively connected to the fluidic cartridge (4 a), (4 b) and (4 c).As already described, the connections (13 b)-(4 b) will assure thefunctions of aspirating the sample from the vessel (5) to the reactionchamber (3) within the fluidic cartridge (1) while the pore connectivity(13 a)-(4 a) will be used to recover the reaction products to the vessel(5′) by injecting air to pouch the eluate out of the reaction chamberinto the recovery tube. Additionally, the connection (13 c)-(4 c) can beused to inject reagents (like but not limited to washing, lysis,binding, enzymes, buffers . . . ) into the fluidic cartridge andtherefore the reaction chamber by the aspiration pump connected to thepore (13 b)-(4 b). As shown in FIG. 3, the reagents are preferablyprovided in disposable containers (15) that are in fluidic connectionwith the manifold.

In a preferred embodiment and as shown in FIG. 3, the reagent disposablecontainers (15) are first introduced in a locking part (18) composedfrom a moving part comprising connecting syringes (20) with a supportingfluidic part (19). The supporting fluidic part (19) comprises fluidtransfer channels associated with each syringe. Each transfer channel ofthe fluidic part is connected to the fluidic manifold (8) by classicaltubing and fittings (not shown). By that, a series of solenoid valves(11) mounted on the manifold will be used to select one specific reagentthat will be transferred from the respective reagent container (15) tothe manifold pore (13c) and thereby be injected into the fluidiccartridge (1).

In preferred embodiment, the manifold can not only used as a support totransfer the sample(s) and the reagents into and from the fluidiccartridge but also to inject reagents or recover eluate into the samplesvessels (5)-(5′). For instance, a reagent can be injected through thepore connectivity (13 c)-(4 c) from a reagent container (15) into thefluidic cartridge to be thereafter transferred in a sample vessel (5) or(5′).

As described by the different embodiments, the disclosed fluidicassembly permit to perform extremely complex assay procedures andreagents combinations in a very simple overall system design.

For more precise positioning and control of the different liquids in thereaction cartridge, in a preferred embodiment of the invention, thefluidic manifold further integrates optical sensors (29), (29′) as shownin FIG. 5. As illustrated in FIG. 7 the optical sensors will be placedon both side of the reaction chamber (3) facing windows of detectionchannels (28) and (28′). The role of the optical sensor (29) is todetect the presence of the liquids in the detection windows (28). Forthat, a standard proximity sensor can be used and that comprises of aphotodiode and a laser diode (LED). As shown in FIG. 8, the presence ofthe liquid in the detection window (FIG. 8 b) channel (28) leads to achange in the reflection of the light emitted by the LED when comparedwith the case liquid absence ((FIG. 8 a). This change of the lightreflection induces a drop of the signal detected by the photodiode incase the liquid is present in the detection window. This sensing processcan be used to determine the position of the liquid upstream anddownstream of the reaction chamber, which is very important of thecontrol and management of the assay procedures.

The liquid position according to the invention is particularly requiredin assays based on magnetic particles where the magnetic particleshandling is particularly sensitive to the presence or absence of theliquid. The magnetic particles handling are preferably handled accordingto the device and the method disclosed in the international patentsapplications WO2008/010111 and WO2008/007270, incorporated herein as areference. Specifically, this method utilizes at least one couple ofelectromagnetic poles having magnetic field sequences having polarityand intensity that vary in time, the role of which is to effectivelybreak or control the particle aggregates and to maintain the particlesin suspension as a fog of particles in relative dynamic motion; and thencombining the magnetic fields from different magnetic poles in asequence to induce displacement of the fog of particles across thereaction chamber whereby the fog of particles occupies substantially thewhole reaction chamber volume. In fact, when the magnetic particles arehomogenously mixed within the reaction chamber it is important to assurethat the chamber is fully filled with liquid to avoid an inadequatefilling during the process.

From the preceded, the invention discloses a fluidic assembly forconducting bioassays which comprises a fluidic cartridge with a reactionchamber and at least one optical sensor positioned on one side of thesaid reaction chamber. In the preferred embodiment, the optical sensoris a proximity planar sensor comprising of an emitting Laser diode (LED)and a detection photodiode. Accordingly, the reaction chamber preferablyfurther comprises magnetic particles that serve as a solid support forperforming the said bioassays.

1.-11. (canceled)
 12. A fluidic cartridge used for extracting targetbiomolecules or particles from a crude sample, the cartridge comprising:a. at least one structure top layer containing: i. a reaction chamberwith a solid support that is designed to capture the said targetbiomolecules, ii. a first inlet and outlet channels that are in fluidcommunication with the said reaction chamber and that will be used tobring the sample it and out the reaction chamber, and iii. a secondinlet and outlet channels connected to the said reaction chamber andthat will be used for eluting the purified biomolecules wherein thesecond inlet and outlet channels are diverging branch of the first inletand outlet channels.
 13. The fluidic cartridge according to claim 12,wherein the solid support is constituted by magnetic particles. 14.(canceled)
 15. The fluidic cartridge according to claim 12, wherein thesaid first inlet channel is in fluid communication with the samplevessel.
 16. The fluidic cartridge according to claim 12, wherein thesaid second inlet channel is in fluid communication with a recoverysample vessel.
 17. The fluidic cartridge according to claim 12, whereinthe reaction chamber is further in fluid communication with a fluidicnetwork channel that brings reagents in the said reaction chamber. 18.The fluidic cartridge according to claim 12, wherein the cartridgefurther comprises a closing down layer composed from a flexible materialand comprising connection pores associated to the ends of said inlet andoutlet channels.
 19. The fluidic cartridge according to claim 15,wherein in processing, the sample is aspirated from the sample vessel,in fluid communication with the first inlet channel, into the reactionchamber through the first outlet channel.
 20. The fluidic cartridgeaccording to claim 16, wherein in processing, the target biomolecules orparticles are eluted into the recovery sample vessel, in fluidcommunication with the second outlet channel, from the reaction chamberby pouching air through second inlet channel.
 21. The fluidic cartridgeaccording to claim 12, which comprises at least one optical sensorpositioned in one side of said reaction chamber.
 22. The fluidiccartridge according to claim 13, wherein the magnetic particles aremanipulated and mixed using at least two electromagnetic poles face eachother across the reaction chamber, and wherein the said magnetic polesare actuated by: a) applying magnetic field sequences having polarityand intensity that vary in time from the electromagnetic poles, whereinsaid magnetic field sequences break or inhibit the particle aggregatesand maintain the particles in suspension as a fog of particles inrelative dynamic movement; and b) combining the magnetic fields fromdifferent magnetic poles in a sequence to induce displacement of the fogof particles across the reaction chamber, wherein the fog of particlesoccupies substantially the whole reaction chamber volume.